Phase I Immunotoxin Trial in Patients with B-Cell Lymphoma

Ellen S. Vitetta, Marvin Stone, Peter Amlot, Joseph Fay, Richard May, Mark Till, Joe Newman, Patty Clark, Robert Collins, D. Cunningham, Victor Ghetie, Jonathan W. Uhr, Philip E. Thorpe

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260 Scopus citations

Abstract

Fifteen patients with refractory B-cell lymphoma were treated in a Phase I dose escalation clinical trial with a highly potent immunotoxin consisting of the Fab’ fragment of a monoclonal anti-CD22 antibody (RFB4) coupled to chemically deglycosylated ricin A chain. All patients had low, intermediate, or high grade non-Hodgkin's lymphoma. The immunotoxin was administered i.v. in two to six doses at 48-h intervals. The peak serum concentration and the t,-_ were not dose dependent among patients and averaged 1.3 Mg/ml and 86 min, respectively. Three patients made antibody against A chain, and a fourth made antibody against both A chain and mouse immunoglobulin. Antibody responses were low (<85 /g/ml)in three patients and were not detected until 1 mo after treatment. The maximum tolerated dose of the immunotoxin was 75 mg/m2. Dose-related toxicities included vascular leak syndrome, fever, anorexia, and myalgia. Dose-limiting toxicities included pulmonary edema and/or effusion, expressive aphasia, and rhabdomyolysis (resulting in reversible kidney failure). There was no evidence of liver dysfunction. Partial responses were achieved in 38% of evaluable patients, and in those patients who had >50% CD22* tumor cells, 50% of the patients achieved a partial response. Clinical responses were not related to tumor grade and were generally transient, lasting between 1 and 4 mo.

Original languageEnglish (US)
Pages (from-to)4052-4058
Number of pages7
JournalCancer research
Volume51
Issue number15
StatePublished - Aug 1991

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Vitetta, E. S., Stone, M., Amlot, P., Fay, J., May, R., Till, M., Newman, J., Clark, P., Collins, R., Cunningham, D., Ghetie, V., Uhr, J. W., & Thorpe, P. E. (1991). Phase I Immunotoxin Trial in Patients with B-Cell Lymphoma. Cancer research, 51(15), 4052-4058.